aDivision of Mycobacterial Research, Medical Research Council National Institute for Medical Research, London NW7 1AA, United Kingdom;bDivision of Medicine, Imperial College London, London W2 1PG, United Kingdom;

cBlizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AB, United Kingdom;aDivision of Mycobacterial Research, Medical Research Council National Institute for Medical Research, London NW7 1AA, United Kingdom;bDivision of Medicine, Imperial College London, London W2 1PG, United Kingdom;

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Abstract

Calcidiol, the major circulating metabolite of vitamin D, supports induction of pleiotropic antimicrobial responses in vitro. Vitamin D supplementation elevates circulating calcidiol concentrations, and thus has a potential role in the prevention and treatment of infection. The immunomodulatory effects of administering vitamin D to humans with an infectious disease have not previously been reported. To characterize these effects, we conducted a detailed longitudinal study of circulating and antigen-stimulated immune responses in ninety-five patients receiving antimicrobial therapy for pulmonary tuberculosis who were randomized to receive adjunctive high-dose vitamin D or placebo in a clinical trial, and who fulfilled criteria for per-protocol analysis. Vitamin D supplementation accelerated sputum smear conversion and enhanced treatment-induced resolution of lymphopaenia, monocytosis, hypercytokinaemia, and hyperchemokinaemia. Administration of vitamin D also suppressed antigen-stimulated proinflammatory cytokine responses, but attenuated the suppressive effect of antimicrobial therapy on antigen-stimulated secretion of IL-4, CC chemokine ligand 5, and IFN-α. We demonstrate a previously unappreciated role for vitamin D supplementation in accelerating resolution of inflammatory responses during tuberculosis treatment. Our findings suggest a potential role for adjunctive vitamin D supplementation in the treatment of pulmonary infections to accelerate resolution of inflammatory responses associated with increased risk of mortality.

Conflict of interest statement: Merck Serono donated €7,000 to Queen Mary University of London in 2010 to support an academic meeting entitled “Vitamin D: Mechanisms of Action in Health and Disease”; this meeting was convened by C.J.G. and A.R.M.

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